1. Field of the Invention
This invention relates to methods for preventing or treating functional gastrointestinal disorder, and relates particularly to a method for preventing or treating functional abdominal pain, irritable bowel syndrome or constipation in a subject.
2. Description of Related Art
Functional gastrointestinal disorders (FGIDs) are the most common problem in gastroenterological practice. These occur as a result of abnormal functioning of the GI tract, and they are defined by chronic abdominal symptom complexes, such as abdominal pain, diarrhea, constipation, and bloating. According to Rome III criteria, more than 20 functional GI disorders have been identified. Common FGIDs include, but are not limited to functional abdominal pain, irritable bowel syndrome (IBS), constipation, functional diarrhea and functional dyspepsia.
Irritable bowel syndrome is a chronic functional gastrointestinal disorder. About 4-30% people worldwide suffer from IBS. IBS has been characterized by two major symptoms: abdominal pain (chronic pain) and bowel habits alteration. According to the predominant symptom, IBS can be classified into four subgroups: IBS with diarrhea (IBS-D), IBS with constipation (IBS-C), mixed IBS (IBS-M), and un-subtyped IBS (IBS-U). In IBS patients, about 30% patients suffer from IBS after gastrointestinal inflammation, and those belong to post-infectious/inflammatory IBS. In addition, the major factor in motivating patients to seek healthcare and causing a significant reduction in quality of life is abdominal pain, which is associated with visceral hypersensitivity (VH). Visceral hypersensitivity is considered to be one of the main mechanisms causing functional gastrointestinal disorders. Moreover, recent studies show that visceral hypersensitivity is highly specific for IBS.
Visceral hypersensitivity is defined as the increased intensity of sensations and the lowered thresholds for visceral pain in patients. The persistent VH is associated with neuronal sensitization, which manifests as an increase in neuronal excitability. Neurotransmitters, such as serotonin (5-hydroxtryptamine, 5-HT), play important roles in neuronal sensitization. Serotonin is a monoamine neuron transmitter. Previous study have shown that awake rats with subcutaneous injection of 5-hydroxytryptophan (5-HTP), a precursor of serotonin, induced VH. The predominant site of serotonin synthesis and storage is the enterochromaffin cells of the intestinal mucosa. Serotonin released from enterochromaffin cells activates neural reflexes associated with intestinal secretion, motility, and sensation. According to clinical studies, patients with IBS are usually accompanied with abnormality of serotonin metabolism. Furthermore, serotonin receptor antagonists have been used widely as a therapeutic drug, indicating that the pathology of IBS is associated with serotonin.
Lowered pain threshold in a rectal distention test, representing visceral hypersensitivity, is a hallmark of IBS patients. In animal studies, colorectal pain threshold can be monitored by electromyography (EMG) signals responded to a barostat distension, and a higher response of EMG signal represents a higher sensitivity to pain. In addition to VH, an increased expression of substance P in the spinal cord has also been demonstrated as a biomarker representing visceral pain sensation during colorectal distension in an IBS rat model.
There are various therapeutic methods to ameliorate symptoms of IBS, including as serotonin receptor antagonists, antidepressant drugs, prokinetics drugs, antispasmodics drugs and probiotics. Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. Due to the absence of pharmacological side effects, probiotics appear to be a potential method for the treatment of IBS. Besides, specific probiotics have been described to confer beneficial effects on constipation symptoms. Probiotics can make host gain healthy benefit via keeping gut flora balance, strengthening mucosal barrier function and modulating immune system. There are lots of evidences indicating that probiotics can act as a therapeutic way of diseases, including infectious diseases, allergy, cancer and necrotising enterocolitis. It is worth to further research the use of probiotics in treating functional gastrointestinal disorders.
Constipation, a worldwide functional gastrointestinal disorder, is defined as infrequent or difficult passage of stool. Constipation has many causes, including chemical compounds, dietary habits, intestinal flora composition, pregnancy, and psychological stress. Although many types of purgative drugs have been identified, most of these drugs have potentially adverse side effects such as inducing tolerance, melanosis coli, or cathartic colon. There is a dysbiosis of the intestinal flora in patients with constipation, which could be improved by consumption of probiotics. Furthermore, probiotic bacteria, especially lactobacilli and bifidobacteria, may lower the pH of the colon, producing lactic acid, acetic acid, and others. A lower pH tends to increase colonic peristalsis and, in consequence, decrease colonic transit time, with a beneficial effect in the treatment of constipation symptoms.
Many studies had show that production and manufacturing methods and the food carrier may influence the properties of probiotic strains, and have an impact on the outcome of clinical intervention studies. Here, we identified a lactic acid bacterium strain under specific manufacturing process (artificial cultured) showed the potential that preventing or treating functional gastrointestinal disorder.